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fgr proto-oncogene mRNA induced in B lymphocytes by Epstein-Barr virus infection
Abstract:
Several acute transforming retroviruses encode tyrosine-specific protein kinases which possess structural and functional relationships to cell-surface receptors for certain growth factors. One such tyrosine kinase is encoded by the onc gene, v-fgr, of Gardner-Rasheed feline sarcoma virus (GR-FeSV). Recently, we have isolated and characterized the human gene, c-fgr, corresponding to the viral onc sequence and have shown that c-fgr is a unique gene located on the short arm of chromosome 1 (ref. 7). Here we report that certain lymphomas (but not sarcomas or carcinomas) express fgr-related messenger RNA. This transcript is detected in Burkitt's lymphoma cell lines naturally infected with Epstein-Barr virus (EBV), but not in EBV-negative Burkitt's lymphoma cells. Normal umbilical cord or peripheral blood lymphocyte lines established in vitro by EBV infection also contain detectable c-fgr mRNA. Moreover, a 50-fold increase of the steady-state c-fgr mRNA concentration is observed when uninfected Burkitt's lymphoma cell lines are deliberately infected with EBV. These findings demonstrate for the first time the induction of a proto-oncogene in response to infection by a DNA tumour virus.
Insights
Epstein-Barr virus (EBV) infection induces the proto-oncogene c-fgr in human lymphomas. This study reveals EBV
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- Acute transforming retroviruses encode tyrosine kinases related to growth factor receptors.
- The v-fgr oncogene from Gardner-Rasheed feline sarcoma virus (GR-FeSV) is a tyrosine kinase.
- The human c-fgr gene, corresponding to v-fgr, is located on chromosome 1.
Purpose of the Study:
- To investigate the expression of fgr-related messenger RNA (mRNA) in human lymphomas.
- To determine the effect of Epstein-Barr virus (EBV) infection on c-fgr mRNA levels.
Main Methods:
- Analysis of fgr-related mRNA in lymphoma cell lines.
- Comparison of c-fgr mRNA expression in EBV-infected versus EBV-negative cells.
- Quantification of c-fgr mRNA levels following deliberate EBV infection.
Main Results:
- Fgr-related mRNA was detected in certain lymphomas, specifically Burkitt's lymphoma.
- c-fgr mRNA was present in EBV-infected Burkitt's lymphoma cells and EBV-infected lymphocyte lines.
- A significant 50-fold increase in c-fgr mRNA was observed upon EBV infection of Burkitt's lymphoma cells.
Conclusions:
- EBV infection induces the expression of the proto-oncogene c-fgr in human lymphomas.
- This is the first demonstration of proto-oncogene induction by a DNA tumor virus.
- c-fgr mRNA expression is linked to EBV status in Burkitt's lymphoma.